Pharmacokinetics is the study of the action of pharmaceuticals and other biologically active compounds from the time they are introduced into the body until they are eliminated. For example, the sequence of events for an oral drug can include absorption through the various mucosal surfaces, distribution via the blood stream to various tissues, biotransformation in the liver and other tissues, action at the target site, and elimination of drug or metabolites in urine or bile. Pharmacokinetics provides a rational means of approaching the metabolism of a compound in a biological system.
One of the fundamental challenges being encountered in drug, environmental, nutritional, consumer product safety, and/or toxicology studies includes the extrapolation of metabolic data and risk assessment from in vitro cell culture assays to animals. Although some conclusions can be drawn with the application of appropriate pharmacokinetic principles, there are still substantial limitations. One concern is that current screening assays utilize cells under conditions that do not replicate their function in their natural setting. The circulatory flow, interaction with other tissues, and other parameters associated with a physiological response are not found in standard tissue culture formats. While in vivo animal models can be used to perform pharmacokinetics (PK)/pharmacodynamics (PD) study, it significantly can increase the cost of the research and the screening throughput is low. Accordingly, there is a strong need in the art for developing alternatives to the use of animal studies, e.g., in vitro models that can better replicate physiological conditions for cells to function in a similar manner as they are present in vivo. Such models can be used, e.g., for PK/PD studies, drug screening, engineered scaffolds for tissue/organ repair or replacement, and/or development of a disease model of interest.